BackgroundLassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease.Methodology/Principal FindingsClinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects.Conclusions/SignificanceLassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.

Endogenous retroviruses of swine are a concern in the use of pig-derived tissues for xenotransplantation into humans. The nucleotide sequence of porcine endogenous retrovirus taken from lymphocytes of miniature swine (PERV-MSL) has been characterized. PERV-MSL is a type C retrovirus of 8,132 bp with the greatest nucleic acid sequence identity to gibbon ape leukemia virus and murine leukemia virus. Constitutive production of PERV-MSL RNA has been detected in normal leukocytes and in multiple organs of swine. The copy numbers of full-length PERV sequences per genome (approximately 8 to 15) vary among swine strains. The open reading frames for gag, pol, andenv in PERV-MSL have over 99% amino acid sequence identity to those of Tsukuba-1 retrovirus and are highly homologous to those of endogenous retrovirus of cell line PK15 (PK15-ERV). Most of the differences in the predicted amino acid sequences of PK15-ERV and PERV-MSL are in the SU (cell attach- ment) region ofenv. The existence of these PERV clones will enable studies of infection by endogenous retroviruses in xenotransplantation.

SARS-coronavirus can infect and replicate within PBMCs of SARS patients, but viral replication in PBMCs seems subject to self-limitation.

Background The COVID-19 pandemic continues to pose an international public health threat. Prevention is of paramount importance to protect the high-risk group of older adults until specific treatments for COVID-19 become available; however, little work has been done to explore factors that promote preventive behaviors among this population. Objective This study aims to investigate the knowledge, perceived beliefs, and preventive behaviors towards COVID-19 of older adults in China and determine the factors that influence their practice of preventive behaviors. Methods From February 19 to March 19, 2020, a cross-sectional, web-based survey was administered to Chinese older adults in all 31 provinces of mainland China using a convenience sampling method to assess the respondents’ knowledge, perceived beliefs, and preventive behaviors towards COVID-19. Standard descriptive statistics and hierarchical linear regression analyses were conducted to analyze the data. Results A total of 1501 participants responded to the survey, and 1263 valid responses (84.1%) were obtained for further analysis. The overall correct rate on the knowledge questionnaire was 87%, overall positive beliefs regarding COVID-19 were found, and the mean behavior score was 13.73/15 (SD 1.62, range 5-15). The hierarchical linear regression showed that respondents who were married or cohabitating and who lived in areas with community-level control measures were more likely to practice preventive behaviors (P<.01). Knowledge (β=0.198, P<.001), perceived susceptibility (β=0.263, P=.03), perceived benefits (β=0.643, P<.001), and self-efficacy in preventing COVID-19 (β=0.468, P<.001) were also found to be significantly associated with preventive behaviors. Conclusions Most older residents had adequate knowledge and positive beliefs regarding COVID-19 and engaged in proactive behaviors to prevent the disease. Knowledge and beliefs were confirmed to be significantly associated with behavior responses. Our findings have significant implications in enhancing the effectiveness of COVID-19 prevention programs targeting the older population; these programs must be continued and strengthened as the epidemic continues.

Th17 cells may contribute to the disease progression and pathogenesis of liver injury in HBV infected patients, and the induction of IL-10 may be one mechanism of constraining pro-inflammatory Th17 responses.

ITX 5061 is a scavenger receptor B1 antagonist that has entered phase 1 clinical trials in hepatitis C virus (HCV)-infected humans. We evaluated ITX 5061 in combination with interferon-α, ribavirin, and HCV protease and polymerase inhibitors in a genotype 2a infectious virus system. ITX 5061 is a potent inhibitor of HCV replication and is additive to synergistic with interferon-α, ribavirin, BILN2061, VX950, VX1, and 2'-C-methyladenosine. Resistance selection experiments were performed using a Jc1-FEO virus co-culture system and intermittent ITX 5061 exposure under neomycin selection. We identified a mutant virus with a substitution of aspartic acid for asparagine at the highly conserved position 415 in E2 (N415D). Introduction of this mutation into wild-type virus conferred high-level resistance to ITX 5061. There was no cross-resistance between ITX 5061 and HCV protease inhibitors or interferon-α. These results suggest that ITX 5061 is a promising compound for study in combination with other HCV inhibitors.

Background/Aims: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. Methods: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4 + and F4/80 + cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-κB in mouse livers and RAW264.7 and EL4 cells were measured. Results: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4 + and F4/80 + cells infiltrating into the liver as well as the activation of p38 MAPK and NF-κB in Con A-treated mouse livers and RAW264.7 and EL4 cells. Conclusion: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4 + and F4/80 + cells and the activation of the p38 MAPK-NF-κB pathway in CD4 + T cells and macrophages.F. Chen contributes to this work equally.

BackgroundDue to the high morbidity and mortality of fulminant hepatitis, early diagnosis followed by early effective treatment is the key for prognosis improvement. So far, little is known about the gene expression changes in the early stage of this serious illness. Identification of the genes related to the very early stage of fulminant hepatitis development may provide precise clues for early diagnosis.ResultsBalb/C mice were used for ConA injection to induce fulminant hepatitis that was confirmed by pathological and biochemical examination. After a gene chip-based screening, the data of gene expression in the liver, was further dissected by ANOVA analysis, gene expression profiles, gene network construction and real-time RT-PCR.At the very early stage of ConA-triggered fulminant hepatitis, totally 1,473 genes with different expression variations were identified. Among these, 26 genes were finally selected for further investigation. The data from gene network analysis demonstrate that two genes, MPDZ and Acsl1, localized in the core of the network.ConclusionsAt the early stages of fulminant hepatitis, expression of twenty-six genes involved in protein transport, transcription regulation and cell metabolism altered significantly. These genes form a network and have shown strong correlation with fulminant hepatitis development. Our study provides several potential targets for the early diagnosis of fulminant hepatitis.